Blood-Brain Barrier Breakdown by Combined Detection of Circulating Tumor and Endothelial Cells in Liquid Biopsy

Blood-brain barrier breakdown occurring in glioblastoma is a temporary condition often denounced by contrast enhancement upon neurological examination. This condition is useful to increase the intracranial concentration of anti-cancer drugs. The prognosis of glioblastoma and its resistance to conventional therapy has stimulated interest in the search of biomarkers able to unmask and monitor brain barrier breakdown to calibrate the treatment. Despite numerous studies had evidenced the role of circulating tumor and endothelial cells to monitor brain tumor, the mechanism of tumor cells release in the bloodstream and its prognostic significance remain unclear. In this chapter, we want to furnish an update on the relationship between the vascular damage occurring during glioblastoma disease and the reactivity of innate immunity focusing on the cytokines network. Our aim is answer to the question: when and why the liquid biopsy is useful in glioblastoma disease

The treatment of hyperuricemia.

AbstractHyperuricemia has long been established as the major etiologic factor in gout. Alongside with an inflammatory state triggered by urate crystal deposition in the joints, hyperuricemia displayed additional pathophysiological consequences leading to tissue inflammation mainly in the vascular wall. Thus, therapeutic strategies used to treat hyperuricemia in the past decades have often been focused on limiting acute episodes. Recently, evidence has been accumulated suggesting that chronic urate deposition requires a correct treatment not limited to acute episodes based on the modulation of the activity of key enzymes involved in metabolism and excretion of urate including xanthine oxidoreductase (XO) and URAT1. The present review article will try to summarize the most recent evidences on the efficacy of XO inhibitors and uricosuric compounds in lowering uric acid levels in both the bloodstream and peripheral tissues. In particular, we will focus on the effect of novel XO inhibitors in counteracting uric acid overproduction. On the other hand, the effect of lowering uric acid levels via XO inhibition will be correlated with attenuation oxidative stress which leads to endothelial dysfunction thereby contributing to the pathophysiology of diabetes, hypertension, arteriosclerosis, and chronic heart failure. Hence, scavenging and prevention of the XO generated oxygen radical accumulation emerge as an intriguing novel treatment option to counteract uric acid-induced tissue damages

Effects of culture system and hypoxia on long-term expansion and differentiation of mesenchymal stem cells derived from periodontal ligament

Periodontal ligament stem cells (PDLSCs), located in the perivascular space of the periodontium were able to differentiate into periodontal cell types in vitro [1]. In this study, we investigated the effect of three different culture media and of low oxygen tension (1%) on the immunophenotype, proliferation rate and osteogenic potential of PDLSCs. This study was the first report to compare the PDLSCs from the same person in different culture systems. PDLSCs were harvested from three healthy third molars and the single-cells suspensions were cultured in the culture media a-MEM, DMEM and a new medium formulation (Enriched Ham’s F12 Medium, EHFM), respectively. PDLSCs were subcultured (4 x 103/cm2) until passage 7. The characterization of PDLSCs included FACS, immunofluorescence analysis and cell proliferation assay in both normoxia and hypoxia (1%). After culture in osteogenic medium for 7, 14 and 21 days, osteoblastic differentiation was evaluated by alkaline phosphatase activity, mineralization (alizarin red staining) and gene expression of osteogenic markers. Osteoblastic differentiation was also evaluated under hypoxic conditions. PDLSCs cultured in EHFM showed increased proliferation rate and CD73 overexpression compared to cells maintained in a-MEM and DMEM. On the other hand, PDLSCs grown in a-MEM and DMEM showed higher osteogenic differentiation potential compared to EHFM. Hypoxia affected both proliferation rate and osteogenic potential. On the basis of these results, we propose a two stages protocol for the osteogenic induction of PDLSCs, in which the early expansion stage could be performed in EHFM without loss of cell stemness. Furthermore, the results obtained in the different conditions (normoxia and hypoxia) suggest that oxygen tension plays a critical role in PDLSCs physiology

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

Measurement of the Jet Mass Distribution and Top Quark Mass in Hadronic Decays of Boosted Top Quarks in pp Collisions at root s=13 TeV

A measurement is reported of the jet mass distribution in hadronic decays of boosted top quarks produced in pp collisions at root s = 13 TeV. The data were collected with the CMS detector at the LHC and correspond to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lepton + jets channel of t (t) over bar events, where the lepton is an electron or muon. The products of the hadronic top quark decay t -> bW -> bq (q) over bar' are reconstructed as a single jet with transverse momentum larger than 400 GeV. The t (t) over bar cross section as a function of the jet mass is unfolded at the particle level and used to extract a value of the top quark mass of 172.6 +/- 2.5 GeV. A novel jet reconstruction technique is used for the first time at the LHC, which improves the precision by a factor of 3 relative to an earlier measurement. This highlights the potential of measurements using boosted top quarks, where the new technique will enable future precision measurements.Peer reviewe

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe